Question

In muscles lactate is considered a waste product under O2 limiting conditions. Under more aerobic conditions lactate can be used as fuel. Briefly outline the metabolic reactions involved in using lactate as a fuel in muscles. Considering these reactions calculate the number of ATP molecules generated from the complete catabolism of lactate to CO2 (use the ATP ratios 2.5 ATP /NADH and 1.5 ATP/FADH for your calculation).

Answer 1

Under anaerobic conditions, pyruvate is reduced to lactate by lactate dehydrogenase (LDH). Lactate is a dead end in glycolysis. NAD+, which is reduced to NADH during the glycolytic pyruvate formation, is then being regenerated by the glycolytic LDH as pyruvate is converted to lactate. Under aerobic conditions, lactate is the main substrate of the TCA cycle. Lactate is transported from the cytosol into the mitochondria via a monocarboxylate transporter, where it is oxidized to pyruvate by mitochondrial Lactate dehydrogenase. Then pyruate goes to TCA cycle and finally converted to CO2.

ATP generation:

Lactate dehydrogenase (1 NADH)= 2.5 ATP

Isocitrate dehydrogenase (1 NADH) = 2.5 ATP

alpha ketoglutarate dehydrogenase (1 NADH) = 2.5 ATP

succinate thiokinase (1 GTP) = 1 ATP

succinate dehydrogenase (1 FADH2) = 1.5 ATP

Malate dehydrogenase (1 NADH) = 2.5 ATP

Total ATP = 12.5 ATP